High iron intake may increase appetite, disease risk

Using an animal model, researchers at Wake Forest Baptist Medical Center have found that dietary iron intake, equivalent to heavy red meat consumption, suppresses leptin, a hormone that regulates appetite.

Iron is the one mineral that humans can't excrete, so the more iron that is consumed the greater the likelihood that leptin levels will drop, resulting in increased appetite and the potential to overeat.

The study was recently published in the Journal of Clinical Investigation.

"We showed that the amount of food intake increased in animals that had high levels of dietary iron," said Don McClain, M.D., Ph.D., director of the Center on Diabetes, Obesity and Metabolism at Wake Forest Baptist and senior author of the study. "In people, high iron, even in the high-normal range, has been implicated as a contributing factor to many diseases, including diabetes, fatty liver disease and Alzheimer's, so this is yet another reason not to eat so much red meat because the iron in red meat is more readily absorbed than iron from plants."

In this study, male mice were fed high (2000 mg/kg) and low-normal (35 mg/kg) iron diets for two months, followed by measuring the levels of iron in fat tissue. The researchers observed a 215 percent increase of iron in the mice fed a high iron diet as compared to the mice fed the low normal diet. In addition, leptin levels in blood were 42 percent lower in mice on the high iron diet compared to those on the low normal diet.

Results from the animal model were verified through ferritin blood tests from a large number of human participants in a previous clinical study. Ferritin blood tests measure the amount of iron stored in the body.

The researchers showed that fat tissue responds to iron availability to adjust the expression of leptin, a major regulator of appetite, energy expenditure and metabolism. "We don't know yet what optimal iron tissue level is, but we are hoping to do a large clinical trial to determine if decreasing iron levels has any effect on weight and diabetes risk," McClain said. "The better we understand how iron works in the body, the better chance we have of finding new pathways that may be targets for the prevention and treatment of diabetes and other diseases."

Funding for the study was provided by the Research Service of the Department of Veterans Affairs and the national Institutes of Health. This study was conducted at the University of Utah before McClain joined Wake Forest Baptist.

Co-authors are Yan Gao, Ph.D., Zhonggang Li, M.S., Scott Gabrielsen, M.D., Ph.D., Judith A. Simcox, Ph.D., Soh-hyun Lee, Ph.D., Deborah Jones, B.S., Bob Cooksey, M.S., and Gregory Stoddard, Ph.D., of the University of Utah; William T. Cefalu, M.D., of Louisiana State University System.